DE102009018545A1 - Method for determining effect of particle beam on partially radiated material, involves partial determining effect of particle beam on material based on microscopic damage correlation from parameter and from property of material - Google Patents

Abstract

The method involves partial determining the effect of a particle beam on the material based on a microscopic damage correlation from a parameter and from a property of the material. The parameter characterizes the particle beam. The microscopic damage correlation takes place in sub micrometer range. Independent claims are also included for the following: (1) a method for the radiation planning for a target volume in a radiation volume by a particle radiation; (2) a method for radiation of the target volume in the radiation volume by a particle radiation; (3) a radiation planning for the radiation volume; (4) a radiation planning device with a computer unit for executing the method; and (5) a beam modification device for a radiation device.

Description

The The invention relates to a method for irradiating a target volume with a particle beam, an irradiation plan, a beam modification device and an irradiation device.

The Irradiation of a target volume in an irradiation volume with Ion or particle beams affect the irradiation of matter, in particular inorganic, organic and biological materials and is used in different fields of research, industry and medical technology. The target volume includes in particular the area in which to modify the irradiated Material should be deposited a predetermined dose; the irradiation volume includes in particular those areas of the material that be penetrated by radiation to the desired dose to reach the target volume. Under a particle beam or ion beam In particular, a high energy beam is either charged Particles, for example protons, carbon ions or ions of others Elements, tines or neutral particles, for example neutrons Understood. In the following description, the terms Ion beam and particle beam sysnonym used. Under high energy In particular, an energy of the particles in the range of a few MeV / amu up to a few GeV / amu (amu: atomic mass unit) understood.

A irradiation device suitable for carrying out the irradiation generally includes an ion beam generating and forming accelerator on, wherein the ion beam for irradiation via a beam transport system in a region in which the irradiation volume is arranged out becomes. Furthermore, the irradiation device comprises a beam modification device, the ion beam in its parameters to the location and size of the target volume.

The Irradiation volume may be, for example, a detector system, which serves for the verification of an irradiation field, wherein the irradiation field usually an area to be irradiated or irradiated in the Covering irradiation volume. In the field of dosimetry will be added For example, films with a photographic emulsion used. Furthermore, nuclear track detectors for measuring the fluence distribution in used the radiation field. In the field of medical applications the irradiation of biological tissue becomes the study of the effect used by particle radiation to reduce the effect of radiation exposure to estimate cosmic rays in space. Finally, the irradiation volume can also be the volume of a tumor in a patient. Ion beams are here used to destroy tumor tissue in the target volume.

at of tumor therapy allow the special properties of ion beams, the tumor tissue with minimal damage to the surrounding to destroy healthy tissue. This depends a favorable depth dose distribution of ion beams together. When penetrating high-energy ion beams in the At first, material deposits them with little energy. With increasing Depth increases the energy deposition, reached in the area of one distribution curve called Bragg peak peaks and falls then steep. This can be done even at lower lying Tumors deposit more energy in the tumor tissue than in the surrounding area healthy tissue.

In the process, ion beams show an effect in the irradiation volume which differs depending on the type of material to be irradiated and on the parameters of the ion beam. In general, ion beams have a different effect than photon radiation. This means that a different dose has to be deposited with ion beams than with photon beams in order to achieve a desired or predetermined effect (irradiation effect) produced by the irradiation with ion beams. In this case, the effective dose is that photon dose D _γ which would lead to the same irradiation effect as the ion dose D _I. The altered effect is observed for both inorganic, organic and biological material. In inorganic materials, lower efficiency of ion beams is observed rather than photon beams. By contrast, when irradiating biological material with ions, a higher efficacy compared to photon irradiation is generally observed.

In front The actual radiation will generally be an irradiation plan for carrying out the irradiation of the target volume, for example of the tumor, created. In the case of irradiation with ion beams should this treatment plan as possible the effect of the ion beams consider.

Different methods for the preparation of an irradiation plan are known. For example, in the publication ( Krämer and Scholz 2000, Physics in Medicine and Biology, Vol. 45, pages 3319-3330 ) describes a method for the preparation of an irradiation plan.

The Effectiveness of the ion beams depends in a complex way the ion type, the ion energy, the irradiation dose, of the irradiated material and each of a considered effect from. The experimental determination of these multiple dependencies with the accuracy necessary for the treatment planning is practically impracticable. That's why models, which allow a prediction of the changed effectiveness, an important tool for the realization of radiation planning These models are usually based on simplifications and Approximations, as the underlying mechanisms of injury of inorganic, organic and biological material not yet are sufficiently cleared up. Accordingly, in the Usually the scope of the models is also limited.

An example of such a model is given in the publication ( Scholz et al, Radiation Environmental Biophysics, Vol. 36, p. 59-66 (1997) ). The model is referred to as LEM, where the term LEM is the abbreviation for "local effect model".

The However, previously known models are usually on a special Ion species, for example carbon ions, optimized. You can no statements for the treatment planning over the entire range of light to heavy ions with sufficient Deliver accuracy.

Therefore there is a need for an option in the form of a model, the effectiveness of ion beams over a wide mass range, especially from protons to neon ions, reliable with to describe and predict the required accuracy.

The Object of the present invention is one opposite the prior art improved method for irradiating a Target volume. Furthermore, an improved method for radiation planning for a target volume to be irradiated be created. Furthermore, an improved irradiation device be created.

The respective task is characterized by the characteristics of the independent Claims solved. Further developments of the proposed Methods and proposed devices emerge the dependent claims.

• – Ermitteln einer Fluenz- und/oder Energieverteilung des Partikelstrahls innerhalb eines das Zielvolumen aufweisende Bestrahlungsvolumen;
• – Ermitteln einer aus der Fluenz- und/oder Energieverteilung resultierenden effektiven Dosisverteilung, wobei Daten verwendet werden, die den beobachtbaren Effekt im Material des Bestrahlungsvolumens zumindest teilweise auf der Basis einer mikroskopischen Schadenskorrelation bestimmen.

The proposed method for irradiating a target volume with a particle beam comprises the steps:

• Determining a fluence and / or energy distribution of the particle beam within an irradiation volume having the target volume;
• - Determining an effective dose distribution resulting from the fluence and / or energy distribution using data that determines the observable effect in the material of the irradiation volume based at least in part on a microscopic damage correlation.

in this connection the target volume is usually a volume to be irradiated in an object. The item may have a delineated volume in a material to be irradiated, for example a detector system, an X-ray film, a phantom for simulating an irradiation situation or be a human. The irradiation volume may be the target volume, in front of the target volume, as well as after the target volume - in Direction of particle beams seen - arranged material be. This is the material of the target volume, for example the material of an article to be modified or the tumor to be destroyed, in the region of the Bragg peak of the particle beam.

The fluence distribution, which usually describes the number of ion or particle passages per unit area (ions / cm ² ) and the associated energy distribution, is hereby usually at least one point of the target volume, but preferably in a three-dimensional (3D) arrangement or matrix of points Target volume determined. The fluence distribution may contain, in addition to the information about the primary ion beams, also information about the secondary particles generated by nuclear reactions.

From the fluence and energy distribution, a resulting macroscopic, physical dose distribution can be determined. The macroscopic physical dose distribution is understood below to mean the dose distribution which results from the expected value of the dose deposition of the particle beams in volumes of typically a few cubic millimeters or greater. This dose distribution is based on knowledge of the number of particles and their energy deposition at each point x _i , y _i , z _{i of} the target volume.

For the description of the expected irradiation effect, however, in the case of ion or particle beams, the macroscopic dose distribution alone is not sufficient. The radiation effect becomes relevant Lich also determined by the changed efficiency of ion beams compared to conventional photon beams.

The The goal of treatment planning is, as a rule, the effective one Dose with an accuracy of about 5-10% determine can. The effective dose is that dose referred to, which would have to be deposited with photon beams, to achieve the same effect as with ion beams. Starting point for Calculation of the treatment plan is therefore the achieved, observable Effect in the material of the target volume. Here are parameters of to be applied ion beams, such as ion beam, Ion beam energies and / or usually the changed Effectiveness used compared to photon beams and from it determines the dose to be applied based on the target volume or calculated.

The LEM according to the prior art makes it possible to derive the effectiveness of ion beams from the knowledge of the physical properties of ion beams as well as the knowledge of the reaction of materials on photon radiation. Due to the simplifications and approximations used, the accuracy of the model is usually only for applications with heavier ions such. As carbon sufficiently accurate for the treatment planning. Based on the original implementation (LEM I), the accuracy of the calculation could be improved by further developments ( LEM II: Elsässer and Scholz 2007, Radiation Research Vol. 167, 319-329 ; LEM III: Elsässer et al. 2008, International Journal of Radiation Oncology Biology Physics, Vol. 71, 866-872 ); However, the model does not yet provide sufficient accuracy for a general application over a wide mass range of ions (proton neon ions) and energy range (1 MeV / u-1 GeV / u).

in the Contrary to the previously used methods in the models LEM I to LEM III becomes microscopic in the proposed method Damage correlation used to determine the effective dose. For the irradiation of non-biological, for example inorganic material are used to determine the changed Effectiveness and thus the effective dose, in particular material constants, such as the sensitivity of silver bromide crystals in X-ray films or staining radiochromic Dyes after irradiation decisive. In the case of irradiation of biological material, such as tumor cells Damage to the DNA contained in the nucleus usually the determining cause of the observable Radiation effects. To describe the effective dose is here often the relative biological effectiveness (RBW) The ion used by the ratio of ion doses is defined to achieve the same effect with photon beams or ion beams are necessary.

Here, the term iso effect is the same effect for D _photon and D _ion . This means that first the type of damage or the observable effect has to be defined and used as a parameter.

Around the dose required to achieve the observable effect be determined, the corresponding material constants or needed to describe the relative biological effectiveness Data preferably in the form of a data set or one of the data containing table.

Examples for such records are tables with parameters for certain ion energies and ion types that determine the allow the relevant RBW values. Of these tables containing Record can be referred to as RBW record and can be in shape a parameter table used to drive an irradiation device is used. But it is also conceivable, the procedure for determining the RBW data set in a control device directly to an irradiation device. The record can be used as a parameter field in a control device for control an irradiation device, for example an accelerator, available.

From the fluence distribution, moreover, the local dose distribution can be determined at any point in a volume of typically 10 × 10 × 10 μm ³ , with a resolution of typically <1 nm ³ , ie in the subnanometer range, in an irradiation field. The local dose distribution can also take into account the spectral distribution of the particles. The local dose distribution is therefore a microscopic dose distribution in contrast to the macroscopic dose distribution defined above.

The determination of the effective dose distribution can be based on the consideration of a local damage correlation, which can be determined with the aid of the local, microscopic dose distribution. The Among other things, the probability of producing correlated damage depends on the number of defects in a subvolume of a suitably selected sensitive volume. In the case of films, the sensitive volume may be defined by the volume of a silver bromide grain; in the case of cells, this may be the cell nucleus. Correlated damage is defined as damage caused by the interaction of individual damage within a suitably chosen distance. As individual damage, for example, polymerization events in a monomer crystal of a GafChromic film or DNA damage in a nucleus of a biological tissue can be considered. The probability of generating correlated damage can therefore be determined, for example, from a distance analysis of the damage. A simple example for determining correlated biological damage is the calculation of the number of double strand break pairs (DNA pairs) within a given distance.

at Previously known methods are the number of damages produced usually not calculated on a (sub) nanometer scale, but instead in micrometer dimension. The calculation is thus generally based on a global information of energy deposition about the corresponding micrometer ranges; this is actually the physical dose location located on the (sub) nanometer scale in the irradiation field too much simplified. Furthermore The previously known methods are generally not based on the transmission the effects of the photon dose-effect curve.

The Combination of precise calculation of spatial Damage distribution (rSv) in nanometer dimensions with reference on the photon dose-effect curve represents a significant innovation of the method proposed here.

Of the The advantage of this method lies in the fact that it is a more accurate calculation of the effective dose is possible and Thus, the treatment planning performed with a significantly improved accuracy can be. In particular, by the method, the accuracy improved at light ions, so the proposed method with equal accuracy over a large area from ions of protons to heavier ions, such as Neon ions, is applicable. In addition, it can affect the effect of ion beams both prospectively during treatment planning as well as retrospectively for the recalculation, review and validation of already prepared and applied treatment plans be taken into account.

The Method is also for determining the effectiveness of neutron beams applicable. When irradiating a target volume with neutrons can generate secondary particles charged by nuclear reactions become. These in turn cause damage in the sensitive Volume. The effect of the neutrons is based on the effect the resulting so-called "recoils" and is characterized by a mixed particle field, which is typically charged particles from protons to oxygen ions. To calculate the effect of this mixed radiation field can Therefore, the same applies to the situation in ion beam therapy Methods are applied.

The the same applies analogously also for other particles.

In An embodiment of the proposed method is the method for the preparation of an irradiation plan of the target volume and / or used to validate an irradiation plan. The treatment plan is usually before the actual irradiation of a target volume determined by calculating a parameter data set that is to Control of the irradiation process stored in an irradiation device can be. The treatment plan can ensure that in the target volume applied the desired effective dose becomes. Due to the fact that at the determined effective dose distribution at least partial data is used, which is specific to the specific Radiation reactions of the irradiated or the material to be irradiated can be an irradiation plan or treatment plan validation generally more precise according to the proposed method be performed. In the special case of tumor irradiation Thus, the effective dose in the tumor can be optimized and thereby the surrounding healthy tissue is optimally protected.

In one embodiment of the method, a microscopic dose distribution is at least partially determined from the fluence distribution. In this case, the microscopic dose distribution, in particular the local dose distribution, can be determined at least with the partial use of the radial dose distribution around a single ion trace. The radial dose distribution describes the expected value of the local energy deposition as a function of the distance from the trajectory of the ion trace. The advantage of using the radial dose distribution is that it can directly refer to the effects after photon irradiation. The radial dose distribution can be generated for example by Monte Carlo simulations. Another possibility is an analytical dose description of an amorphous web structure.

In a further refinement of the method, the microscopic, spatial damage distribution (rSv) is determined at least partially from the microscopic dose distribution (mDv), the probability of a local damage induction required therefor being derived at least partially from an associated photon dose-effect curve (PEK1). The photon dose effect curves per se are known and are usually determined experimentally. For example, the average number of defects can often be described by a linear-quadratic relationship: N _damage = γD _X + δD _X. Here, D _X is the X-ray or photon dose and γ and δ are material-specific constants, such as polymerization events in a monomer crystal of a GafChromic film or parameters for the yield of double-strand breaks.

The Effect of photon beams is characterized by the fact that the Spatial distribution of the resulting damage due to the physical properties of the energy deposition of photons uniformly stochastically distributed. If the sensitive volume in sub-volumes, also referred to as parcels, is divided, one can assume that each parcel the has the same damage density distribution. This means that one even damage distribution in each plot is present.

On the other hand, for a sensitive volume irradiated with ions, which is divided into parcels, a heterogeneous distribution of damage exists due to the extremely localized energy deposition of ion beams. If the sensitive volume is divided into parcels having a size of less than or equal to 1 × 1 × 1 nm ³ (≦ 1 × 1 × 1 nm ³ ) and the microscopic dose, in particular local microscopic dose distribution, determined in each parcel, can thus microscopic, spatial damage distribution rSv be determined.

In An embodiment of the method is at least partially the spatial, microscopic damage distribution of Expected value for the number of correlated damages (AkS) in a suitably selected subvolume of a sensitive Volume determined more accurately. Here, the term "correlated Damage ", meant by the damage caused by the spatial Interaction of individual damage may arise. The spatial Correlation can be done by analyzing the distances the individual damages are defined. In the case of biological Material can do a correlated damage for example through the combination be defined by two single-strand breaks of DNA, the lead to a DNA double-strand break or two double-strand breaks, that cause damage to the biological Material is bad to repair. The advantage of using Correlated damage is due to the fact that Thus, in particular the non-linear reaction of materials or Cells on irradiation can be better taken into account.

In Another embodiment of the method is the material in Irradiation volume at least partially a biological material. The material may in this case be composed of cells, cell cultures and / or Tissues, for example tumor tissue include. The volume can however at the same time contain other material, such as a Metal implant included with biological tissue.

In a further embodiment of the method, the sensitive Volume at least partially at least one lower and / or partial volume of the biological material, in particular a cell. The sensitive Volume has in particular a partial volume of a cell. It can preferably a nucleus. The extent of the sensitive volume to determine the local, microscopic dose distribution can accordingly correspond to the typical dimensions of a cell, ie in about 10 microns. For the subdivision of the sensitive Volume in the parcels described above can increase the resolution here in the range of nanometers, d. H. the dimension of a The parcels described above are on the order of magnitude of typically ≤ 1 nm. The advantage of viewing on the nanometer scale is due to the fact that at a sufficiently fine resolution the microscopic dose within a plot as a first approximation as constant can be accepted. This assumption allows the effect of Energy deposition of ion beams within a plot Derive the dose-effect curve for photon radiation.

In a further embodiment of the method, a photon dose (PD1) is determined which would have been required to achieve the same yield of correlated damage, ie the same number of correlated damages (AkS) with respect to the total number of individual injuries, such as after ion irradiation. This means that, for a macroscopic photon dose within the irradiation field, a spatial distribution of the damage, the type and number of which according to the photon dose effect curve PEK1, is determined, from which the expected value of the number of correlated damages can be determined. In particular, this results in a photon dose PD1, which leads to the same yield of correlated damage as after ion radiation. For example, for the expected value of the number of double-strand break pairs within a given distance, one can assume that this square depends on the macroscopic photon dose hangs. In particular, this allows a rapid determination of PD1 based on the simulation of the yield of correlated damage at a given photon dose. For this it is assumed that with sufficiently small selected plots and with the same local dose with photon and with ion irradiation a similar damage is induced. This can also be explained by the fact that, given a sufficiently small plot volume, even in the case of ion beams, the expected value of the energy deposition in this volume can be assumed to be homogeneously distributed and thus directly comparable to the effect of the irradiation of photon beams. It is advantageous here that the number of damage known from photon irradiation can be transferred to an ion-irradiated material in this dimension.

In a further embodiment of the method, at least in part an effect (E1) associated with the photon dose (PD1) is determined from a second photon dose-effect curve for the observable effect (PEK2). In contrast to the photon dose-response curve (PEK1), which describes the local, microscopic or molecular damage, the photon dose-response curve (PEK2) represents the macroscopically observable effect. In the case of cells PEK2 z. For example, characterize the inactivation of cells, for example characterized by the linear-quadratic parameters α _X and β _X known for many cell and tissue types. In the case of tissues or organs, PEK2 may describe the likelihood of tissue damage or organ failure. An advantage similar to PEK1 is that by referring to the experimental photon data, PEK2, a high accuracy of the detected biological effects for ion irradiation can be achieved. Furthermore, with this method compared to others. Process the computing times are drastically reduced.

wobei beispielsweise angenommen werden kann, dass E1 durch ein einzelnes Ion mit zugehöriger Dosisdeposition ID und zugehöriger PD1 entstanden ist.In a further preferred embodiment of the method, the observable effect (E2) for the given fluence distribution is at least partially derived from the scaling of the biologically relevant effect (E1) corresponding to the ratio of the photon dose (PD1) and the dose deposited in the sensitive volume according to the fluence distribution (E1). ID). In particular, the observable effect (E2) can be calculated as follows:

for example, it may be assumed that E1 has been produced by a single ion with associated dose deposition ID and associated PD1.

wobei α_int·ID_single dem biologischen Effekt eines einzelnen Ions mit Dosisdeposition ID_single entspricht. Gemäß der Veröffentlichung ( Krämer und Scholz, Physics in Medicine and Biology, Vol. 51, S 1959–1970, 2006. ) lässt sich β_int aus α_int gewinnen und aus α_int und β_int für das gesamte gemäß der Fluenzverteilung erzeugte gemischte Strahlenfeld letztlich der Effekt E2. Dabei kann der Effekt nach Ionenbestrahlung beispielsweise mittels der linear-quadratischen Parameter α_ion und β_ion beschrieben werden.In a further embodiment of the method, the effective dose is determined at least partially from the photon dose (PD2) associated with the observable effect (PKE2). By means of suitable optimization methods, the ion dose for each point of the irradiation field can thus be selected such that a predetermined effect can be achieved in each point of the irradiation volume. For example, in the case of a mixed radiation field, PD2 may also be determined from consideration of the radiation field at each point of the radiation field according to methods known in the art. In particular, the so-called intrinsic RBW of individual ions can be used, wherein the intrinsic RBW can be determined as follows:

where α _int · ID _single corresponds to the biological effect of a single ion with dose position ID _single . According to the publication ( Krämer and Scholz, Physics in Medicine and Biology, Vol. 51, pp. 1959-1970, 2006. ), β _int can be obtained from α _int , and finally, from α _int and β _int for the entire mixed radiation field produced according to the fluence distribution, the effect E 2. In this case, the effect after ion irradiation can be described, for example, by means of the linear-quadratic parameters α _ion and β _ion .

The advantage of the method is that it allows a direct transfer of the experience with conventional irradiation to the irradiation with particle beams. A further advantage of the proposed method is that the RBW _int values are predicted in advance independent of the current radiation field for individual ions from protons to neons for energies of 0.1 MeV / u to 1 GeV / u and known as RBW tables Tables can be stored before E2 is calculated for the mixed radiation field. This can lead to a further considerable savings in computing time.

The object is further achieved by an irradiation plan for the irradiation of a target volume having irradiation volume, the irradiation plan at least partially using the The method described above is erectable and / or was set up. In the preparation of the treatment plan, therefore, data are used which determines the effective dose distribution resulting from a fluence distribution, wherein the relevant observable effect in the material of the irradiation volume based at least in part on the macroscopic damage correlation, and in particular on the number of correlated damage (AkS ), is determined.

The Task is further by a radiation modification device solved using the above described Method for irradiation of a target volume produced and / or is operable. The beam modification device can in this case have an active and / or passive device for performing of the procedure is set up.

A active beam modification device can in this case, for example a raster scan device that detects the particle beam according to a Location and energy parameter field leads over the target volume. A passive beam modification device can in this case, for example a filter element, which by means of the proposed method was designed or manufactured. The filter element on this Fashion has been designed, then can be used in an irradiation facility to be built in. Here, by means of the filter element a Energy and thus the penetration depth (z-direction) of the ion or Particle beam to be modified while each of the x- and y-direction by deflecting the beam by means of a Be scanned scanner. Thus, by interaction of the passive filter element and the active scanner to be irradiated Target volume to be scanned.

The The object is further achieved by an irradiation device, which has at least one beam modification device which includes the features described above. Here, the Irradiation device, in particular an accelerator device for generating and accelerating a particle beam and a beam modification device, by means of a to irradiated target volume scanned in all three spatial directions can be. In this case, the beam modification device can both passive as well as active as well as a combination of passive and active active facilities to change the beam energy and Have jet position and / or beam axis at the location of the target volume. The irradiation device preferably has a control system for Control of the accelerator device and the at least one Beam modification device for irradiating objects, especially patients, on. This allows the irradiation device controlled by the control system, the control system has a device in which an irradiation plan is stored or with which a corresponding treatment plan is generated can.

The The invention has been described in terms of preferred embodiments and emphasizes that equivalents, alternatives and modifications of the objects and / or features in the Scope of the protection area are included, as long as these are not outside the scope of the claims.

following The invention will be more apparent from the figures of the drawing described. This will be for similar items the same reference numbers are used in the figures. Show it:

1 a schematic representation of a principle of operation of a beam modification device and its effect on a depth dose distribution;

2 1 is a schematic representation of an irradiation device with an active beam modification device (FIG. 2a ) and with a passive beam modifier; ( 2 B )

3 a schematic representation of a microscopic dose distribution in a sensitive volume for irradiation with ions ( 3a . 3b . 3c ) and photons ( 3d );

4 a flowchart of a method for irradiating a target volume;

5 a flowchart of method steps, which in the in 4 shown method can be explained in more detail;

6 a distribution of DNA damage in a sensitive volume after irradiation with ions and photons;

7 a distribution of DNA damage in a sensitive volume after photon irradiation, resulting in the same yield of correlated damage as in 6 shown irradiation with ions;

8th a function of an RBW factor as a function of the linear energy transfer (LET);

9a a schematic representation of a radiation dose applied with helium ions in a target volume as a function of the penetration depth;

9b a representation of a cell survival as a function of the depth of penetration in a target volume after irradiation with the irradiation field 9a ;

10a a schematic representation of an applied with protons and carbon ions irradiation dose in a target volume in the case of a typical two-field irradiation

10b a schematic representation of the calculated cell survival and the associated experimentally determined survival probabilities for the irradiation of a target volume with the radiation fields from 10a ,

1 schematically illustrates a beam modification device 10 and their effect on a monoenergetic ion or particle beam 12 dar. The monoenergetic ion beam 12 is by means of arrows 14 shown with the same length schematically. The arrows 16a to 16i represent ion beams of different energy and thus an ion beam 16 which is not monoenergetic, that is, has ions of different energies. In the lower part of the 1 in each case a schematic diagram is shown, which shows a Bragg peak 18 (left illustration), 24 (right) in a material to be irradiated (not shown) showing the relative dose as a function of the depth of penetration in the material. The relative dose is on an axis called y-axis 20 plotted and the penetration depth on an axis designated as x-axis 22 , The curve of the Bragg peak 18 describes the course of the dose as a function of depth for irradiation with monoenergetic ions. The Bragg Peak 24 describes the relative dose in the material as a function of the penetration depth for an ion beam 16 with the arrows 16a to 16i represented different energies. The Bragg Peak 24 is called an extended Bragg peak 24 denotes and consists of a superposition of individual Bragg peaks 19a to 19i for each one by the arrows 16a to 16i symbolically represented energy of the ion beam 16 together. The ion beam 16 can in this case by means of the beam modification device 10 from the ion beam 12 be generated. The relative dose corresponds to a deposited dose in an irradiation volume (not shown). The zero point 26 the x-axis 22 corresponds to the surface of the irradiation volume.

Here is the effect of the beam modification device schematically 10 shown, with the aid of which a target volume (not shown) can be irradiated with a predetermined dose distribution. For this purpose, a monoenergetic beam through active or passive beam guiding elements of the beam modification device 10 with respect to the beam energy and penetration depth modulated so that a predetermined depth range can be occupied with the desired dose. The arrow 28 symbolizes the effect of the beam modification device 10 starting from the Bragg peak 18 for monoenergetic ion irradiation towards the Bragg peak 24 for the ion beam 16 ,

2 represents various implementation possibilities of the beam modification device 10 represents. 2a shows a schematic representation of a structure of an irradiation device or particle therapy system 30 constructed accelerator device 36 with an active beam modification device 32 which includes active beam guidance and beam application. The particle therapy system 30 typically has a particle beam 34 generating beam generating device 38 and a beam accelerator 40 on. The beam generating device 38 typically has a particle source, for example an ion source. The beam acceleration device typically has a low-energy accelerator unit and an associated beam guide. The accelerator device 36 Downstream is a synchrotron 42 , a cyclotron or other accelerator and a high-energy beam transport device. After the synchrotron 42 becomes a particle beam 34a provides the energy necessary for irradiation. Particles or particles such as protons, tines, helium ions, carbon ions, oxygen ions or other charged particles or particles of chemical elements or compounds called ions are typically used as particles. Thus, the terms ions, particles and particles are used interchangeably in the invention.

In 2 is an example of the ion source 38 , a linear accelerator 40 and a synchrotron 42 shown. The accelerator device 36 and the downstream high energy accelerator may also comprise any other accelerator capable of producing a particle beam 34a , in particular from charged ions, with the for the irradiation of a target volume 44 provide necessary energy. For use in tumor therapy are typically accelerators 36 used an ion beam 34a with a maximum energy of the particles of the order of typically 1 GeV / amu.

The target volume 44 is in an object or irradiation volume 46 arranged, with the object 46 that the target volume 44 surrounding volumes and / or the entire object to be irradiated. The target volume to be irradiated 44 may be any shaped volume to be exposed to particle radiation, for example, a film detector system, a cell culture filled volume, or a tumor volume in a patient (not shown). The target volume 44 can both a resting target volume 44 as well as a moving target volume 44 be. The target volume 44 is typically sliced 45a . 45b . 45c . 45d . 45e . 45f split, each with an ion beam 34a with one for each disc 45a . 45b . 45c . 45d . 45e and 45f necessary specific energy to be irradiated. The respective energy is usually with the Sysnchrotron 42 set and is variable.

To be administered total dose in the target volume to be irradiated 44 , becomes the target volume 44 For example, it is irradiated by means of a raster scan method, whereby a thin pencil beam is generated by means of deflection magnets 48a and 48b such as 50a and 50b lateral over the volume to be irradiated 46 steered, by varying the high-energy accelerator setting or the absorber thickness, the beam energy and thus the penetration depth of the beam 34a varies and the beam so that in the longitudinal direction over the volume to be irradiated, in particular on the discs 45a . 45b . 45c . 45d . 45e and 45f guided.

The irradiation device 30 has a flow control device 52 and at least one detector 54 for monitoring the parameters of the ion beam called ion beam parameters 34a on. The flow control device 52 is by means of a typically electrical connection 56 with the accelerator device 36 , in particular the synchrotron 42 , and by means of a connection 58 with a raster scan device 60 coupled. By means of a connection 62 is the flow control 52 with the detector 54 connected. Thus, over the detector 54 determined values (parameters of the particle beam 34a ), such as energy and position of the particle beam 34a , for controlling and regulating the irradiation device 36 , in particular the synchrotron 42 , be used. The detector 54 can be made up of several detector units. In the embodiment shown, the detector is 54 from two detector units 54a and 54b compounded and therefore assigns the connection 62 two connections 62a and 62b on. An example of a detector 54 for the determination of the ion beam parameters is for example an ionization chamber 54a and a multi-wire proportional chamber 54b which are usable or suitable as beam intensity or beam position monitors.

The flow control device 52 represents the control system of the particle beam system 30 and thus controls the individual components of the system 30 such as the accelerator device 36 , the synchrotron 42 and the magnets 48a . 48b such as 50a and 50b the raster scan facility 60 , Further, in the flow control device 52 Measurement data, such as data of the detector 54 , are read in and / or stored for monitoring the beam parameters.

Usually, the control of the beam parameters of the particle beam system takes place 30 with the help of an irradiation plan, which is generated before an irradiation. This treatment plan will typically be before the start of irradiation of the target volume 44 created in a planning facility. However, it can also be provided to create and / or modify the treatment plan when the irradiation has already begun. By means of a procedure 200 (in 4 dargstellt) such irradiation plans can be created.

In the 2a shown beam modification device 10 is an active beam modification device 32 , The arrangements of in 2a shown components of the particle beam system 30 are only examples. Other arrangements, in particular other components for beam generation and beam modifications can be used.

2 B shows a schematic representation of an example of another embodiment of an irradiation device 66 , The modulation of the beam energy (energy of the ion beam) is in this case via a so-called. Ridge filter system 68 , The shape of this filter 68 is designed so that by variable thickness at different points of the filter an ion beam 34a is braked differently strong. By the construction of the filter 68 thus becomes the exact form of the depth dose distribution of the ion beam in the target volume 44 clearly defined. Conversely, a given depth dose distribution determines the design of the associated filter 68 , The technical design of the filter 68 is thus typically determined by the respective Irradiation plan dependent. The procedure 200 for the preparation of an irradiation plan can in the manufacture of the filter system 68 and / or individual components can be used and thus z. B. are used to generate control data for CNC manufacturing machines. The data of the effective dose distribution to be achieved by the proposed method can thus be used in the production of the filter 68 be used. In the 2 B shown beam modification device 10 is called a passive beam modifier 70 designated. The passive beam modification device 70 typically includes next to the filter 68 a collimator device 71 , of which schematically only one collimator is shown.

Next the above-described active and passive method of beam modification are also mixed methods for implementing a beam modifier conceivable.

3 shows schematically the expected value of the energy deposition on a micrometer scale for photon beams ( 3d ) and ion beams ( 3b ). The changed effect of ion beams compared to photon radiation can be attributed to the different microscopic distribution of the energy deposition 72 of the different types of radiation, ie ion radiation and photon radiation. In the case of photon radiation, this distribution takes place on average uniformly over a considered area 74 , In contrast, ions deposit their energy very heterogeneously distributed. Near a trajectory or track 76 of an ion (at a few nm distance) extremely high doses D (up to approx. 10 ⁶ Gy) can be deposited, whereas at larger distances (a few μm) the trajectory can be deposited 76 the dose values can very quickly drop to very low values (<< 1 Gy). This results in a very heterogeneous distribution overall 78 ( 3b ) of the deposited energy. However, considering only a small subrange (nm ³ ) 80 ( 3c ) of this heterogeneous distribution 78 Thus, the dose deposited in this sub-area can again be assumed to be approximately constant. Thus, this distribution is similar to the distribution expected for irradiation with photons at the same local dose.

Thus, by selecting a suitable subarea 80 due to the similarity described above, the effect of ion beams in a small portion are derived from the action of photon radiation. In particular, a sensitive volume is selected as partial area, in particular as partial volume.

The exploitation of this principle for calculating the effect of ion beams for the determination and optimization of an irradiation plan will be described in the following with reference to FIG 4 illustrated method explained in more detail.

4 shows a flowchart of a method 200 for the preparation of an irradiation plan for the irradiation of the target volume 44 with the particle beam 34a (see 2 ) is used. In process step 210 the calculation is started. In the process step 220 becomes a fluence distribution in a target volume 44 the irradiation volume 46 determined. The target volume 44 may comprise an inorganic, organic or biological material to be irradiated. Biological material is typically composed of cells. The target volume 44 For example, it may have at least one cell culture and / or at least one tissue, for example a tumor tissue.

In process step 230 an effective dose distribution resulting from the fluence distribution is determined using data which determines the effect observable in the respective material on the basis of a microscopic, in particular local, damage correlation. In step 235 it is queried whether the desired target dose is achieved for the given fluence distribution. If this is the case, the procedure in step 240 completed. If this is not the case, the fluence distribution is modified according to the difference between the setpoint and actual values of the effective dose distribution and then to step 220 continued.

The procedure 200 can be used to irradiate the target volume 44 , for drawing up an irradiation plan, which is based on the irradiation of the target volume 44 is used, and / or for validation of the treatment plan before or after irradiation of the target volume 44 be used.

The procedure 200 includes in the process step 230 the use of a biophysical model, since the use of particle beams in the irradiation of matter, in particular of biological tissue in tumor therapy, requires the exact knowledge of the biological effects of particle beams. The biophysical model used is referred to as the local effect model (LEM) and takes into account the complex dependence of the effectiveness of parameters of the particle beam 34a , such as type of particle (ion species), ion beam energy, ion dose and material, in particular cell or tissue type. Hereby, the biological effect of the local energy deposition becomes in the calculation of the effective dose distribution taken into account within a cell or a cell nucleus.

5 shows a flowchart of the method steps in the process step 230 of the flowchart of 4 may be included.

wobei λ eine Normierungskonstante ist, LET den linearen Energietransfer beschreibt, r_min den inneren Bereich mit konstanter Dosis charakterisiert und r_max der maximale Spurradius ist, beispielsweise bestimmt durch: rm = γEδ (5)mit γ = 0.062, δ = 1.7. r_max ist hierbei gegeben in μm und E ist die spezifische Energie des Ions in MeV/u. Der LET bezeichnet hierbei die von einem Ion pro Weglängeneinheit bei Durchgang durch wasseräquivalentes Material deponierte Energie und wird in keV/μm angegeben.In the process step 250 From the fluence distribution a microscopic dose distribution mDv is determined. In this case, the microscopic dose distribution, in particular the local dose distribution, can be determined at least with the partial use of the radial dose distribution around a single ion trace. The radial dose distribution describes the expected value of the local energy deposition as a function of the distance from the trajectory of the ion trace. The advantage of using the radial dose distribution is that it can directly refer to the effects after photon irradiation. The radial dose distribution can be generated for example by Monte Carlo simulations. Another possibility is an analytical dose description of an amorphous web structure. The radial dose distribution describes the expected value of the local energy deposition as a function of the distance from the trajectory of the ion trace. The advantage of using the radial dose distribution is that it can directly refer to the effects after photon irradiation. The radial dose distribution can be generated for example by Monte Carlo simulations. Another possibility is an analytical dose description of an amorphous web structure. in the form used in the LEM models known in the art:

where λ is a normalization constant, LET describes the linear energy transfer, r _{min characterizes} the inner region with constant dose and r _{max is} the maximum track radius, for example determined by: r m = γE δ (5) with γ = 0.062, δ = 1.7. Here, r _max is given in μm and E is the specific energy of the ion in MeV / u. The LET designates the energy deposited by one ion per path length unit when passing through water-equivalent material and is given in keV / μm.

In the process step 260 a spatial damage distribution rSv is at least partially determined from the microscopic dose distribution mDv, wherein the probability of a local damage induction is at least partially derived from an associated photon dose effect curve PEK1. In the case of biological target volume, z. As cells or tissues, the spatial damage distribution rSv can be given for example by the distribution of double-strand breaks (DSB) in the nucleus. In this case, the associated photon dose-effect curve PEK1 is the dose-effect curve describing the induction of double-strand breaks as a function of the dose.

In the process step 270 the expected value for the number of correlated damages in a suitably chosen volume is determined at least in part from the spatial damage distribution rSv within a sensitive volume. In the case of biological material, the sensitive volume has at least one lower and / or partial volume of a cell of the biological material. As described above, the advantage of the division into a subvolume and / or subvolume lies in the fact that in a subarea the distribution of the expected value of the energy deposition is almost uniform even with ion beams, and thus resembles the distribution in photon beams.

Therefore the biological effect in those small volumes should be that correspond to that for photon radiation at the same size Dose expected.

Consequently it is thereby made possible the biological effect of Derive ion beams from that of photon rays.

In the process step 280 For example, a photon dose PD1 that would have been required to achieve the same yield of correlated damage is determined. The correlated damages are typically combinations of double-strand breaks induced within a given distance. As correlated damage but also combinations of double-strand breaks with single-strand breaks or at whose damage to the DNA relevant to the cell functions is considered.

In the process step 290 is determined from a second photon dose-effect curve PEK2 for the observable effect, an effect E1 associated with the photon dose PD1. For example, when irradiating tumor tissue, the observable effect may be tumor destruction. The observable effect may also affect the surrounding healthy normal tissue; For example, it may be the damage to the skin that lies in the entrance channel of the radiation field in front of the tumor. The photon dose-effect curve PEK2 in these cases would represent a dependency of the tumor destruction or the skin damage as a function of the irradiation dose.

In the process step 300 For example, an observable effect E2 for the given fluence distribution is determined from the scaling of the observable effect E1 according to the ratio of the photon dose PD1 and the ion dose ID deposited in the sensitive volume in accordance with the fluence distribution.

In the process step 310 For example, the effective dose is determined to be that photon dose PD2 that would result in the same E2 effect as the ion dose ID. The relative biological effectiveness then results from the ratio of the photon dose PD2 to the ion dose ID.

With the procedure 200 predictions can be made about observable effects, such as the probability of survival of cells in irradiated cell culture, the likelihood of tumor destruction, or the likelihood of normal tissue damage following irradiation with a particle beam 34a do.

Typically, with the method 200 the effect is correctly described over the entire energy range relevant for use in tumor therapy as well as over a wide range of different ionic species. Sample calculations using the procedure 200 have been performed are shown and described in the following figures.

• 1) Der Zellkern als sensitives Volumen wird als Zylinder mit einem Volumen von 500 μm³ simuliert. Der Zellkernradius wird mittels experimenteller Daten bestimmt. Die Zellkernhöhe ergibt sich entsprechend.
• 2) Die radiale Dosisverteilung um einzelne Ionenspuren ergibt sich gemäß Gleichung (4). Dabei ist r_min = v/c·6.5 nm energieabhängig, wobei v die Ionen- und c die Lichtgeschwindigkeit sind.
• 3) PEK1 wird aus experimentellen Daten zu N_DSB = γ_DSB·D_γ mit γ_DSB = 30 DSBs/Gy/Zelle und D_γ ist die Photonendosis. Zusätzlich wird ein weiterer Clustereffekt von Einzelstrangbrüchen (ESB) wie in ( Elsässer und Scholz 2007, Radiation Research Vol. 167, 319–329 ) berücksichtigt.
• 4) PEK2 ergibt sich aus:
  
  wobei α, β die linear-quadratischen Parameter sind, die in der Regel durch „in-vitro”-Messungen oder klinische Daten gegeben sind. s = α + 2βD_t ist die Steigung oberhalb eines Schwellwertes D_t, oberhalb dessen nach experimenteller Kenntnis die PEK2 in einen rein exponentiellen Verlauf übergeht. S_t ist die Steigung für D > Dt und η quantifiziert den Clustereffekt von ESB (siehe oben und Elsässer und Scholz 2007, Radiation Research, Vol. 167, 319–329 ).
• 5) Korrelierte Schäden werden in den Beispielrechnungen als DSB-Paare mit einem Abstand kleiner als 440 nm angesehen. Dieser Wert wurde unter Anwendung des erfindungsgemäßen Verfahrens anhand experimenteller Daten optimiert. Er ist unabhängig von Ionensorte, Ionenenergie, Dosis oder biologischem Material.

The calculations may be based on the following descriptions and parameters, which are not necessarily for the proposed determination of the effective dose distribution:

• 1) The nucleus as a sensitive volume is simulated as a cylinder with a volume of 500 μm ³ . The nucleus radius is determined by means of experimental data. The cell nucleus height results accordingly.
• 2) The radial dose distribution around individual ion traces is obtained according to equation (4). In this case, r _min = v / c · 6.5 nm is energy-dependent, v being the ion velocity and c the speed of light.
• 3) PEK1 is calculated from experimental data for N _DSB = γ _DSB × D _γ with γ _DSB = 30 DSBs / Gy / cell and D _γ is the photon dose. In addition, another cluster effect of single-strand breaks (ESB) as in ( Elsässer and Scholz 2007, Radiation Research Vol. 167, 319-329 ) considered.
• 4) PEK2 results from:
  
  where α, β are the linear-quadratic parameters, which are usually given by "in vitro" measurements or clinical data. s = α + 2βD _t is the slope above a threshold value D _t , above which, according to experimental knowledge, the PEK2 changes into a purely exponential curve. S _t is the slope for D> Dt and η quantifies the cluster effect of ESB (see above and Elsässer and Scholz 2007, Radiation Research, Vol. 167, 319-329 ).
• 5) Correlated damages are considered in the example calculations as DSB pairs with a distance smaller than 440 nm. This value was optimized using the method according to the invention on the basis of experimental data. It is independent of ion type, ion energy, dose or biological material.

6 shows a calculated distribution of double-strand breaks after irradiation of a nucleus with a radius of 5 μm with an ion (11 MeV / u, 153.5 keV / μm) or photons. For both types of radiation, the same total energy deposition D ₁ = 0.3 Gy was used, which corresponds to the dose position of the individual ion in the cell nucleus. The three axes x, y, z each represent a longitudinal extension of the cell nucleus in the x-direction, y-direction and z-direction, wherein the numerical value corresponds to a length in micrometers. The circular symbols 98 each represent a double-strand break after crossing an ion through the nucleus, whereas the quadratic symbols 99 one double strand break after Be radiation with photons. The trajectory or trajectory of the ion as such is indicated by the arrow 97 characterized. It can be clearly seen that the double-strand breaks are located after ion irradiation in a narrow region around the ion trajectory. The double-strand breaks after photon irradiation, with the symbol 99 are stochastically and approximately uniformly distributed throughout the cell nucleus volume.

by virtue of the different spatial distribution is for it Ion beams much more likely, correlated damage, d. H. for example, two double-strand breaks within one predetermined distance of, for example, 440 nm to induce.

When Measure of the probability of induction correlated Damage can be more correlated with the ratio of number Damage, for example double-strand break pairs (DSB pairs), to the total number of induced individual injuries (DSB) become. To deal with photon rays a similar relationship the number of correlated damage AkS to the total number of Individual damage as induced by ion beams is a much higher dose is necessary.

7 shows the calculated distribution of double-strand breaks 99 after photon radiation at a dose that leads to the same ratio of correlated damage to total damage as that in 6 shown distribution for ion beams. For a suitably chosen subvolume of the nucleus, therefore, the in 7 shown distribution as representative of the effect of a 6 be viewed ion beam and thus the effect of an ion beam derived from the action of conventional photon beams. The model based on this technique is called a generalized local effect model (GLEM).

In 8th shows a calculation of the relative biological activity for the inactivation of HSG (human salivary gland) cells after irradiation with helium and carbon ions carried out with the help of the GLEM. The relative biological activity (RBW) is plotted on the y-axis as a function of the linear energy transfer (LET) on the x-axis. The underlying photon data for PEK2 (α = 0.313 Gy ^-1 , β = 0.0615 Gy ^-2 were ( Furusawa et al. 2000 Radiation Research, Vol. 154, pp. 485-496 ), D _t = 18 Gy, and the nucleus radius is 5 μm.

The curves 85 and 92 denote a functional relationship between the maximum RBW factor RBW _α = α _ion / α _x and the LET for irradiation with helium and carbon ions calculated according to the method GLEM and a comparison with experimental data 90 and 96 (exp. data taken from Furusawa et al. 2000 Radiation Research, Vol. 154, pp. 485-496 ). Curve 85 is one according to GLEM, curve 86 according to LEM III and curve 88 is a calculated according to LEM II curve for helium ions. The measurement data denoted by round symbols and represented by 90 are those that are after irradiation of a target volume 44 were determined with helium ions. Analog shows curve 92 a calculation with GLEM, curve 93 with LEM III and curve 94 shows a calculation with LEM II for carbon ions; and the square symbols symbolized by 96 , show the associated experimental values. It is clear that the curve 85 and the curve 92 best reflect the experimental values. Especially for a low LET, it can be clearly seen that the curves calculated with GLEM are the position of the measured values 90 and 96 predict better.

This is done by the in 9 shown comparison. 9a shows a physical dose profile 81 for a volume irradiated with energy-modulated helium ions (4 cm extended Bragg peak at a water-equivalent depth of 8 cm) as a function of the penetration depth x in mm. With the reference number 79 is the one in the target volume 44 deposited dose D called. The arrows 100 denote the ion beam. As a comparison with experimental data, the experimentally determined survival of CHO cells is compared with the parameters of PEK2 α = 0.228 Gy ^-1 , β = 0.02 Gy ^-2 and D _t = 35 Gy (nucleus radius 5 μm) with the calculated survival.

In 9b turns curve 87 a result of the calculation according to LEM I, curve 82 according to the calculation according to LEM II, curve 78 according to the calculation with LEM III, and curve 84 according to the calculation in accordance with the GLEM. The filled circles, marked by 83 , represent the experimental results (publication Müller, GSI Report 2004 ). Again, the calculation with GLEM shows a much better match with the experimental data compared to the models LEM I-LEM III.

10 shows in a further comparison the calculation of the effect of protons and carbons in a therapy-like irradiation field together with the corresponding experimental data for CHO cells with the also experimentally determined PEK2 parameters α = 0.105 Gy ^-1 , β = 0.025 Gy ^-2 and D _t = 40 Gy (nuclear radius 6 μm).

10a shows the physical dose distribution with two opposing fields radiated at an angle of 180 degrees. The irradiation of the target volume 44 with the particle beam 34a is here from a first direction, by the arrows 100 is shown schematically, and a second direction by the arrows 110 is shown schematically takes place. Curve 116 shows a physical dose profile D of the carbon irradiation and curve 118 a physical dose profile D of proton irradiation. The dose is denoted by D and plotted on the y-axis and the unit of length x on the x-axis. The location of the target volume 44 is through the area 112 shown schematically.

10b shows the calculated and experimentally determined survival of CHO cells. The square symbols 124 are the measured survival and the curve 114 the calculated survival after proton irradiation. The round icons 122 represent the measured survival and the curve 120 the calculated survival after carbon irradiation. From the comparison of the curve 114 with the measurement results 124 for a proton radiation and the comparison of the curve 120 with the measured data 122 It can be seen that the effective dose distribution using the model GLEM with the proposed method 200 which gives very good experimental data.

The comparisons in the 8th - 10 thus show that the calculations using the model GLEM according to the invention are most suitable for predicting the effective dose distribution, in particular for particle therapy.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited non-patent literature

• Krämer and Scholz 2000, Physics in Medicine and Biology, Vol. 45, pp. 3319-3330 [0008]
• Scholz et al, Radiation Environmental Biophysics, Vol. 36, pp. 59-66 (1997) [0010]
• - LEM II: Elsässer and Scholz 2007, Radiation Research Vol. 167, 319-329 [0021]
• - LEM III: Elsässer et al. 2008, International Journal of Radiation Oncology Biology Physics, Vol. 71, 866-872 [0021]
• Krämer and Scholz, Physics in Medicine and Biology, Vol. 51, p. 1959-1970, 2006. [0044]
• - Elsässer and Scholz 2007, Radiation Research Vol. 167, 319-329 [0095]
• Elsässer and Scholz 2007, Radiation Research, Vol. 167, 319-329 [0095]
• - Furusawa et al. 2000 Radiation Research, Vol. 154, pp. 485-496 [0100]
• - Furusawa et al. 2000 Radiation Research, Vol. 154, pp. 485-496 [0101]
• - Müller, GSI Report 2004 [0103]

Claims (15)

Method for irradiating a target volume ( 44 ) with a particle beam ( 34a ), comprising the steps of: determining a fluence and / or energy distribution within a target volume ( 44 ) irradiation volume ( 46 ); Determining an effective dose distribution resulting from the fluence and / or energy distribution, using data showing the observable effect in the material of the irradiation volume ( 46 ) determined at least in part on the basis of microscopic damage correlation. A method according to claim 1, characterized in that the method for the preparation of an irradiation plan of the target volume ( 44 ) and / or to validate an irradiation plan for the target volume ( 44 ) is used. A method according to claim 1 or 2, characterized in that from the fluence distribution at least partially a microscopic dose distribution is determined. Method according to one of the preceding Claims, in particular according to claim 3, characterized in that a spatial microscopic Damage distribution at least partially from the microscopic dose distribution is determined, with the probability of local damage induction at least partially from an associated photon dose effect curve is derived. Method according to one of the preceding Claims, characterized in that the expected value for the number of correlated damage in one selected sub-volume of a sensitive volume at least partly from the spatial, microscopic damage distribution is determined. Method according to one of the preceding claims, in particular claim 5, characterized in that the material in the irradiation volume ( 46 ) at least partially a biological material. Method according to one of the preceding Claims, in particular according to claim 5 or 6, characterized in that the sensitive volume at least Partially at least one sub and / or partial volume of the biological Material, in particular a cell having. Method according to one of the preceding Claims, in particular claim 7, characterized that a photon dose is determined to reach the same Yield of correlated damage according to the Ion beams expected value of the number of correlated damage would have been necessary. Method according to one of the preceding Claims, in particular claim 8, characterized that from a second photon dose effect curve for the observable effect at least partially to the photon dose proper effect is determined. Method according to one of the preceding Claims, in particular claim 9, characterized that an observable effect for the given fluence distribution at least partially from the scaling of the observable effect according to the ratio of the photon dose (PD1) and in the sensitive volume according to the fluence distribution deposited dose is determined. Method according to one of the preceding Claims, characterized in that the effective dose at least partially from that of the observable effect Photon dose is determined. Radiation plan for irradiation of a target volume ( 44 ) irradiation volume ( 46 ), characterized in that the treatment plan is at least partially determined using a method ( 200 ) can be set up according to any one of claims 1-11 and / or was set up. Beam modification device using a method ( 200 ) can be produced and / or operated according to one of claims 1-11. Beam modification device according to claim 13, comprising a unit, in particular an active beam modification device ( 32 ) and / or a passive beam modification device ( 70 ) designed and / or arranged such that a method ( 200 ) according to one of claims 1 to 11 is feasible. Irradiation device, the at least one beam modification device ( 10 ) according to claim 13 or 14.